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Vaccination with Toxoplasma gondii calcium-dependent protein kinase 6 and rhoptry protein 18 encapsulated in poly(lactide-co-glycolide) microspheres induces long-term protective immunity in mice.

Zhang NZ, Xu Y, Wang M, Chen J, Huang SY, Gao Q, Zhu XQ - BMC Infect. Dis. (2016)

Bottom Line: However, no effective vaccine is yet available.Poly(lactide-co-glycolide) polymers can reduce protein degradation and sustain the release of antigens over a long period, which could generate a long-lasting immune response in vivo.Further comparison of the immune responses to the proteins adjuvanted with PLG or Montanide™ ISA 206 VG 6 weeks after the last immunization revealed that antigens encapsulated in PLG conferred greater protective immunity against challenge.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu Province, 730046, PR China.

ABSTRACT

Background: Toxoplasmosis is a worldwide zoonosis caused by the intracellular parasite Toxoplasma gondii. However, no effective vaccine is yet available. Poly(lactide-co-glycolide) polymers can reduce protein degradation and sustain the release of antigens over a long period, which could generate a long-lasting immune response in vivo. Using a mouse model of toxoplasmosis, we evaluated the protective efficacy of vaccination with two recombinant proteins, which are formulated in biodegradable polymers.

Methods: Two recombinant proteins, rCDPK6 and rROP18, were encapsulated in poly(D,L-lactide-co-glycolide) (PLG), and then injected subcutaneously into Kunming mice. The mice immune responses were evaluated in terms of lympho-proliferation, cytokine expression, and antibodies. The survival of infected mice and brain cyst formation were also evaluated at 6 weeks after challenge with T. gondii RH strain (genotype I) or PRU strain (genotype II).

Results: Both protein vaccines induced Th1-biased immune responses, with increased specific antibodies and T cells, high levels of interferon-γ and interleukin 2, and strong lymphocyte proliferative responses. The mice immunized with the various protein vaccines survived slightly longer time than the control groups (P > 0.05) after injection with T. gondii RH strain. There were fewer brain cysts in the mice in all the immunized groups than that in the control groups, and the brain cysts were significantly reduced in mice immunized with proteins + 206, rCDPK6 + PLG and rCDPK6 + rROP18 + PLG (P < 0.05) compared controls. Further comparison of the immune responses to the proteins adjuvanted with PLG or Montanide™ ISA 206 VG 6 weeks after the last immunization revealed that antigens encapsulated in PLG conferred greater protective immunity against challenge.

Conclusions: These findings suggest that the two recombinant T. gondii proteins encapsulated in PLG conferred immunity to T. gondii for an extended period, providing the foundation for the further development of a commercial vaccine against toxoplasmosis.

No MeSH data available.


Related in: MedlinePlus

Number of tissue cysts per brain after challenge with Toxoplasma gondii cysts in mice from all groups. Mice immunized with various protein vaccines and in controls were challenged with 10 tissue cysts of T. gondii PRU strain, 6 weeks after the last booster. The 4 control groups, PBS + PLG, PBS + 206, PBS and blank control, were treated as controls in statistical analysis. The P value was calculated using the measurements from each immunized group to compare with the average from controls. Furthermore, the numbers of brain cysts in mice immunized with various proteins were compared with that in controls. ***P < 0.001
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Fig6: Number of tissue cysts per brain after challenge with Toxoplasma gondii cysts in mice from all groups. Mice immunized with various protein vaccines and in controls were challenged with 10 tissue cysts of T. gondii PRU strain, 6 weeks after the last booster. The 4 control groups, PBS + PLG, PBS + 206, PBS and blank control, were treated as controls in statistical analysis. The P value was calculated using the measurements from each immunized group to compare with the average from controls. Furthermore, the numbers of brain cysts in mice immunized with various proteins were compared with that in controls. ***P < 0.001

Mentions: As shown in Figure 6, immunization with the different proteins partially protected the mice against chronic T. gondii infection. The tissue cyst loadings in the brains of mice vaccinated with the various proteins varied from 47.7 % to 73.6 %, and were significantly lower than those in the control groups (P < 0.001). The protein antigens plus PLG microparticles provided more effective protection to the mice than was observed in the corresponding groups of mice immunized only with proteins. However, the differences were not statistically significant (P > 0.05).Fig. 6


Vaccination with Toxoplasma gondii calcium-dependent protein kinase 6 and rhoptry protein 18 encapsulated in poly(lactide-co-glycolide) microspheres induces long-term protective immunity in mice.

Zhang NZ, Xu Y, Wang M, Chen J, Huang SY, Gao Q, Zhu XQ - BMC Infect. Dis. (2016)

Number of tissue cysts per brain after challenge with Toxoplasma gondii cysts in mice from all groups. Mice immunized with various protein vaccines and in controls were challenged with 10 tissue cysts of T. gondii PRU strain, 6 weeks after the last booster. The 4 control groups, PBS + PLG, PBS + 206, PBS and blank control, were treated as controls in statistical analysis. The P value was calculated using the measurements from each immunized group to compare with the average from controls. Furthermore, the numbers of brain cysts in mice immunized with various proteins were compared with that in controls. ***P < 0.001
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4836102&req=5

Fig6: Number of tissue cysts per brain after challenge with Toxoplasma gondii cysts in mice from all groups. Mice immunized with various protein vaccines and in controls were challenged with 10 tissue cysts of T. gondii PRU strain, 6 weeks after the last booster. The 4 control groups, PBS + PLG, PBS + 206, PBS and blank control, were treated as controls in statistical analysis. The P value was calculated using the measurements from each immunized group to compare with the average from controls. Furthermore, the numbers of brain cysts in mice immunized with various proteins were compared with that in controls. ***P < 0.001
Mentions: As shown in Figure 6, immunization with the different proteins partially protected the mice against chronic T. gondii infection. The tissue cyst loadings in the brains of mice vaccinated with the various proteins varied from 47.7 % to 73.6 %, and were significantly lower than those in the control groups (P < 0.001). The protein antigens plus PLG microparticles provided more effective protection to the mice than was observed in the corresponding groups of mice immunized only with proteins. However, the differences were not statistically significant (P > 0.05).Fig. 6

Bottom Line: However, no effective vaccine is yet available.Poly(lactide-co-glycolide) polymers can reduce protein degradation and sustain the release of antigens over a long period, which could generate a long-lasting immune response in vivo.Further comparison of the immune responses to the proteins adjuvanted with PLG or Montanide™ ISA 206 VG 6 weeks after the last immunization revealed that antigens encapsulated in PLG conferred greater protective immunity against challenge.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu Province, 730046, PR China.

ABSTRACT

Background: Toxoplasmosis is a worldwide zoonosis caused by the intracellular parasite Toxoplasma gondii. However, no effective vaccine is yet available. Poly(lactide-co-glycolide) polymers can reduce protein degradation and sustain the release of antigens over a long period, which could generate a long-lasting immune response in vivo. Using a mouse model of toxoplasmosis, we evaluated the protective efficacy of vaccination with two recombinant proteins, which are formulated in biodegradable polymers.

Methods: Two recombinant proteins, rCDPK6 and rROP18, were encapsulated in poly(D,L-lactide-co-glycolide) (PLG), and then injected subcutaneously into Kunming mice. The mice immune responses were evaluated in terms of lympho-proliferation, cytokine expression, and antibodies. The survival of infected mice and brain cyst formation were also evaluated at 6 weeks after challenge with T. gondii RH strain (genotype I) or PRU strain (genotype II).

Results: Both protein vaccines induced Th1-biased immune responses, with increased specific antibodies and T cells, high levels of interferon-γ and interleukin 2, and strong lymphocyte proliferative responses. The mice immunized with the various protein vaccines survived slightly longer time than the control groups (P > 0.05) after injection with T. gondii RH strain. There were fewer brain cysts in the mice in all the immunized groups than that in the control groups, and the brain cysts were significantly reduced in mice immunized with proteins + 206, rCDPK6 + PLG and rCDPK6 + rROP18 + PLG (P < 0.05) compared controls. Further comparison of the immune responses to the proteins adjuvanted with PLG or Montanide™ ISA 206 VG 6 weeks after the last immunization revealed that antigens encapsulated in PLG conferred greater protective immunity against challenge.

Conclusions: These findings suggest that the two recombinant T. gondii proteins encapsulated in PLG conferred immunity to T. gondii for an extended period, providing the foundation for the further development of a commercial vaccine against toxoplasmosis.

No MeSH data available.


Related in: MedlinePlus